Prospective (e‐diary) vs retrospective (<scp>ARIA</scp>) measures of severity in allergic rhinoconjunctivitis: An observational compatibility study
Authors: Stephanie Dramburg, Serena Perna, Marco Di Fraia, Salvatore Tripodi, Stefania Arasi, Sveva Castelli, Danilo Villalta, Francesca Buzzulini, Ifigenia Sfika, Valeria Villella, Ekaterina Potapova, Maria Antonia Brighetti, Alessandro Travaglini, Simone Pelosi, Ulrike Grittner, Paolo Maria Matricardi
Journal: Allergy (2022)

To the Editor, Severity assessment in relation to allergen exposure is an essential part of the diagnostic work-up for seasonal allergic rhinoconjunctivits (AR). Regularly recorded patient-reported symptom data may support the physician's decision-making on etiological diagnosis and therapeutic success of a pharmacological treatment or allergen-specific immunotherapy (AIT).1 Although several mobile applications facilitate the prospective collection of symptom data via e-diaries, severity measures often still rely on retrospective questionnaires and studies on data quality and validation in longitudinal data sets are scarce.2, 3 In this analysis, we aim to investigate whether and how prospectively acquired measures of disease severity (e-diary) relate to those retrospectively assessed via the Allergic Rhinitis and its Impact on Asthma (ARIA) questionnaire4 in grass pollen allergic patients. Within the observational @IT.2020 pilot project, 91 patients (average age 13.7 years (SD 3.2), 58/91 (64%) male) with a diagnosis of seasonal AR living in Rome, Italy, provided complete data sets for all study visits and recorded symptoms, medication intake and quality of life measures via the AllergyMonitor® e-diary app.5 Symptom severity was assessed with daily Symptom Score (dSS),6 Combined Symptom Medication Score (CSMS),6 and Visual Analogue Scale (VAS)3 and these prospective outcomes were compared to the retrospective ARIA severity classification obtained after the pollen season. For our analysis, we used the (i) cumulative dSS/CSMS/VAS; (ii) average dSS/CSMS/VAS; and (iii) number of "high days," surpassing the arbitrarily chosen thresholds of ≥1 for dSS (max. 3), ≥2 for CSMS (max. 6) and ≥3 for VAS (max. 10). We tentatively divided the severity of AR in our study population as mild (n = 40, 44%), moderate (n = 38, 42%), and severe (n = 13, 14%), according to criteria reported in Table S3. These categories based on prospective monitoring (e-diary) matched in 46/91 (50%) those retrospectively generated by ARIA classification. Extreme inconsistencies were only observed in 4/91 (5%) patients. Moreover, the impact of symptoms on quality-of-life, prospectively measured by daily questions on sleep, work, and daily activity (Figure 1), significantly related to the retrospective classification in mild, moderate, and severe AR. For the frequency of symptoms, the observed differences were more heterogeneous. While patients who retrospectively judged their AR symptoms as persistent, indicated to suffer from allergic symptoms during more than 50% of the recorded days (Figure 1, bottom left), those retrospectively assessing their symptoms as intermittent, showed a broader range of data entries indicating symptoms. This is also reflected in a match/mismatch-analysis between ARIA criteria and e-diary data (Figure 1, bottom right). Interestingly, only 47% (43/91) of the patients showed a match of their retrospective and prospective frequency classification. The largest mismatch group (41/91, 45%) retrospectively judged their symptoms as persistent, while the e-diary entries reflected an intermittent phenotype. To support the intuitive interpretation of prospectively collected severity data for physicians, we propose a comprehensive bubble chart (Figure 2). This scattergram visualizes for each individual patient (=bubble) the three most frequently used parameters to measure AR severity: (i) symptom score (dSS, x-axis); (ii) symptom-medication score (CSMS, y-axis); and (iii) impact on QoL (VAS, diameter of each bubble). Bubble colors and positions within the graph area give a quick overview on AR severity for individuals and the patient cohort. The use of e-diaries to investigate AR severity in a routine setting is still in its infancy. We show that the prospective and retrospective assessment of AR severity are well interrelated, suggesting reciprocal consistency and cross-compatibility. However, our results suggest, that patients remember with less precision the frequency rather than the severity of their symptoms. Further, we propose an observer-friendly interpretation of patient-reported severity measures. More studies are required to develop this novel method, investigating its strengths, weaknesses, and optimal use in routine allergy practice. SD data analysis, manuscript preparation and writing, SP data management and data analysis, MdF/SA/SC/DV/FB/IS/VV/EP/MAB/AT/SP data acquisition, review of the manuscript, ST data acquisition, critical review of the manuscript. UG statistical analysis and critical review, PMM data acquisition, supervision of statistical analysis, writing, and critical review of the manuscript. The @IT.2020 pilot project was supported by an unrestricted educational grant from Euroimmun (code 118583). We thank all participants and the entire study team. SA was supported by the EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology. The study has been supported by an unrestricted grant from Euroimmun (code 118583). The Informatics Platform "AllergyCARD" (eCRF) and the APP "AllergyMonitor®" (eDiary) have been provided by TPS Production (Rome, Italy). These companies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Matricardi reports grants and personal fees from Euroimmun AG, during the conduct of the study, grants and personal fees from Thermo Fisher Scientific, personal fees from Hycor Biomedical Inc, outside the submitted work. Salvatore Tripodi and Simone Pelosi are co-founders of TPS Software Production. Simone Pelosi reports personal fees from TPS Software Production. All other authors declared no conflicts of interest. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.